34(D-4) メリラクトンAの全合成(口頭発表の部)

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Merrilactone A (1) was isolated from pericarps of Illicium merrillianum. Because of its neurotrophic activity, 1 is expected to possess therapeutic potential to treat neurodegeneration associated with Alzheimer's and Parkinson's diseases. Apart from the biological aspects, the highly oxygenated and caged pentacyclic skeleton of 1 serves interesting synthetic challenges. In this paper, we report the efficient total synthesis of (±)-1. The construction of cis-bicyclo[3.3.0]octane framework embedded within 1 was envisioned to involve the desymmetrization of meso-diketone 3 through an intramolecular aldol reaction. Eight-membered meso-diketone 3 was efficiently prepared through pairwise symmetrical functionalizations from commercially available 2 in nine steps. In the crucial intramolecular aldol reaction, the reaction conditions and the protecting groups of 3 were found to significantly affect the diastereoselectivity. When the dichlorobenzyl (DCBn) protected 3d was treated with base 13, the desired isomer 4d was obtained as an exclusive isomer. Thus, this single reaction remarkably established the relative stereochemistry of four chiral centers (C4, C5, C6, C9). In regard to the total synthesis of 1 from 4d, the proper orchestration of the functional group manipulation was the most critical issue. The key transformations included (i) radical cyclization to set the highly congested C9 quaternary center (18→19), (ii) stereoselective reduction of C7-ketone utilizing the rationally designed enol ether (24→25), (iii) regioselective oxidation of tetraol (26→27), and (iv) acid-treatment of α-epoxide 29, which gave rise to the targeted merrilactone A (1).
天然有機化合物討論会の論文
2004-10-01

34(D-4) メリラクトンAの全合成(口頭発表の部)

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